A multidisciplinary study is proposed to isolate, characterize and reverse the action of the primary gene product in the inherited disease, cystic fibrosis. The projects comprising this will include (A) isolation and characterization of the ciliary inhibitor from saliva, and media from cultured cells derived from cystic fibrosis patients and heterozygotes, (B) investigation of growth and cytokinetic characteristics of cystic fibrosis cells in vitro, (C) ultrastructural and histocytochemical studies of cystic fibrosis cells and tissues, (D) cytogenetic and cell hybridization studies of cystic fibrosis cells in vitro, and (E) studies on the relationships of surface membranes and selected enzymes to the cystic fibrosis factor. Collective objectives are to obtain fundamental understanding of the primary defect and to test and apply the information obtained to the treatment of cystic fibrosis. Research methods include conventional protein isolation and primary structure analysis, isoelectric focusing, cilia assays, cell culture and cloning, cell hybridization, cytogenetics, electron microscopy, histocytochemistry, enzyme activity determination, electrophoresis, membrane protein characterization, immunochemical techniques including immunoelectron microscopy.